在鼻咽癌患者中，使用辅助性自体肿瘤浸润淋巴细胞（TILs）联合同步放化疗（CCRT）的一期研究中观察到了安全性和客观的临床反应。共156例III-IVb期，术前Epstein-Barr病毒DNA水平≥4000拷贝/毫升的患者被随机分配接受CCRT联合TIL输注（n = 78）或仅接受CCRT（n = 78）。所有患者都接受了CCRT，被分配到TIL组的患者在CCRT后1周内接受了TIL输注。主要终点是研究者评估的3年无进展生存率（PFS）。随访中位时间为62.3个月后，CCRT联合TIL输注组和仅CCRT组的3年PFS率之间没有显著差异（分别为75.6%和74.4%，危险比为1.08，95%置信区间为0.62-1.89）。TIL输注是安全的，没有3级或4级不良事件，所有高级别不良反应与CCRT引起的骨髓抑制有关。探索性分析显示，在循环CD8 + TIM3 +细胞水平、血清IL-8或PD-L1较低的患者中，TILs可能具有生存益处。在具有良好疗效的患者中，TIL产品与干扰素-γ的转录增加以及一系列与炎症相关的基因和较低的枯竭评分相关。在高危NPC患者中，CCRT联合TILs延长PFS的主要目标并没有达到。这些发现可能为未来评估基于CCRT的TIL联合免疫检查点抑制剂组合的试验设计提供证据。NCT02421640。版权所有©2023 Elsevier公司。保留所有权利。

The safety and objective clinical responses were observed in the phase I study using adjuvant autologous tumour-infiltrating lymphocytes (TILs) following concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients.One hundred fifty-six patients with stage III-IVb and pretreatment Epstein-Barr virus DNA levels of ≥4000 copies/ml were randomly assigned to receive CCRT combined with TIL infusion (n = 78) or CCRT alone (n = 78). All patients received CCRT and patients assigned to the TIL group received TIL infusion within 1 week after CCRT. The primary endpoint was investigator-assessed progression-free survival (PFS) at 3 years.After a median follow-up of 62.3 months, no significant difference was observed in the 3-year PFS rate between the CCRT plus TIL infusion group and CCRT alone group (75.6% versus 74.4%, hazard ratios, 1.08; 95% confidence intervals, 0.62-1.89). TIL infusion was safe without grade 3 or 4 adverse events and all the high-grade adverse effects were associated with myelosuppression caused by CCRT. Exploratory analysis showed that a potential survival benefit was observed with TILs in patients with lower levels of circulating CD8+TIM3+ cells, serum IL-8 or PD-L1. The infused TIL products in patients with favourable outcomes were associated with increased transcription of interferon-γ and a series of inflammatory related genes and a lower exhausted score.The primary objective of prolonging PFS with CCRT plus TILs in high-risk NPC patients was not met. These findings may provide evidence for the design of future trials investigating the combination of TILs plus immune checkpoint inhibitors based on CCRT in high-risk NPC patients.NCT02421640.Copyright © 2023 Elsevier Ltd. All rights reserved.